Human hepatocellular carcinoma (HCC) is usually asymptomatic at early stages. As a result, HCC is generally at an advanced stage when discovered, and the therapeutic options very limited. HCC is associated with chronic liver injury, primarily chronic viral hepatitis and alcoholic liver disease. The risk of developing HCC is 50 - 100 fold greater in individuals with chronic hepatitis B virus infection than in non-infected individuals, and the incidence of HCC in cirrhotic carriers of hepatitis C virus (HCV) may be as high as 5% per year. In principle, therefore, screening protocols are justified for chronic HBV carriers and cirrhotic HCV patients. The only molecular marker that has been widely used for the diagnosis and detection of HCC is alfafetoprotein (AFP). However, AFP expression is significantly increased in a considerable number of patients with non-malignant chronic liver diseases. Thus, more specific markers for HCC are required. Results recently obtained in this laboratory have shown that a protein called glypican-3 (GPC3) can be detected in most HCC tissue sections but it is undetectable in normal liver or benign liver disease. In addition, examination of a limited number of patients has shown that whereas GPC3 is undetectable in the serum of healthy individuals, its levels are significantly elevated in a large proportion of HCC patients. These results suggest, therefore, that GPC3 could be a better marker than AFP for the diagnosis and detection of HCC. The main goal of this study is to test this hypothesis. To this end, serum GPC3 and AFP will be measured in a cohort of 100 patients with HCC, and in patients with benign liver disease. The specificity and sensitivity of both markers will then be compared. GPC3 levels will also be assessed in 50 additional tissue sections from HCC patients, and a similar number of sections from various benign liver diseases. Another objective of this project is to investigate whether GPC3 could be used as a marker of tumor burden in experimental cancer. If this is the case this study will provide a tool that will simplify the search of novel treatments for HCC, and may open the possibility of using GPC3 measurement for the follow-up of HCC patients. [unreadable] [unreadable]